Oximinophosphonodithioates

ABSTRACT

COMPOUNDS HAVING THE FORMULA   R-C(-R1)=N-O-P(=S)(-R2)-S-CH2-R3   IN WHICH R IS (1) ALKYL OR (2) LOWER ALKYLTHIOMETHYL; R1 IS ALKYL; R2 IS ALKYL; AND R3 IS (1) YDROGEN, (2) LOWER ALKYLTHIO, (3) CYANO, (4)PHENYLTHIO, (5) SUBSTITUTED PHENYLTHIO WHEREIN THE SUBSTITUTENT IS HALOGEN, (6)   -CO-NH-R4   WHEREIN R4 IS HYDROGEN OR ALKYL,(7) HALOPHENYL, (8) PHTHALIMIDO, (9) VINYL, (10) CARBOALKOXY, (11) ALKYL, (12) EHTYNYL, (13) CCI2=CR5-WHEREIN R5 IS HYDROGEN OR CHLORINE, (14)-CH2OC(O)NH(LOWER ALKYL) OR (15) BENZYLTHIO, THEIR USE AS INSECTICIDES AND ACARICIDES, PROCESS FOR PREPARING THE COMPOUNDS, INTERMEDIATES AND A PROCESS FOR PREPARING INTERMEDIATES.

United States Patent 01 t'fice 3,755,425 OXIMINOPHOSPHONODITHIOATES Arnold D. Gutman, Berkeley, Calif., assignor to Stautfer Chemical Company, New York, N.Y.

N Drawing. Original application Apr. 6, 1970, Ser. No. 26,148. Divided and this application Mar. 9, 1972, Ser. No. 233,330

Int. Cl. C07f 9/38 US. Cl. 260-5025 2 Claims ABSTRACT OF THE DISCLOSURE Compounds having the formula in which R is (1) alkyl or (2) lower alkylthiomethyl; R is alkyl; R is alkyl; and R is (1) hydrogen, (2) lower alkylthio, (3) cyano, (4) phenylthio, (S) substituted phenylthio wherein the substitutent is halogen, (6') 0 i J-NHR wherein R is hydrogen or alkyl, (7) halophenyl, (8) phthalimido, (9) vinyl, (10) carboalkoxy, (11) alkyl, (12) ethynyl, (13) CCl =CR wherein R is hydrogen or chlorine, (14) -CH OC(O)NH(lower alkyl) or (15) benzylthio, their use as insecticides and acaricides, process for preparing the compounds, intermediates and a process for preparing intermediates.

S SCH -R in which R is (1) alkyl having 1 to 8 carbon atoms, preferably branched chained, more preferably methyl and t-butyl or (2) lower alkylthiomethyl having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms; R is alkyl having 1 to 4 carbon atoms, preferably methyl; R is alkyl having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms and R is (1) hydrogen; (2) lower alkylthio having 1 to 4 carbon atoms; (3) cyano; (4) phenylthio; (5-) substituted phenylthio wherein the substitutent is halo, preferably chloro; (6) the radical wherein R is hydrogen or alkyl having 1 to 4 carbon atoms, preferably methyl; (7 halophenyl, preferably dichlorophenyl; (8) phthalimido; (9) vinyl; carboalkoxy having 1 to 5 carbon atoms; (12) ethynyl; (13) CC1 =CR wherein R is hydrogen or chlorine; (14) -CH OC(O)NH(lower alkyl) or benzylthio.

3,755,425 Patented Aug. 28, 1973 The compounds of the present invention can be prepared according to the following reactions:

in which R, R R and R are as defined.

In the event that the desired compound cannot be prepared because of difficulty of preparing or obtaining the compound HSCH R of Reaction I(b), then the following reaction can be utilized to obtain the compounds of this invention.

in which R, R R and R are as defined and X is chlorine, bromine, or iodine. The compound recited in Reaction I(a), and I(b) when R is lower alkylthiomethyl having 1 to 4 carbon atoms and R is alkyl having 1 to 4 carbon atoms, if not obtainable can be prepared according to the following reaction:

III(a) O O RSH ClOH f'lR RSCH flR III(b) O RSCH; g NaHCOs RSCH; R HzNOH-HCI C=N-OH Preferably, Reaction I(a) is carried out by reacting excess of either reactant is used, the reaction still proceeds but yields are reduced. The reactants can be combined in any desired manner but preferably, the reaction is run in a solvent such as THF by first preparing the salt of the oxime reactant with an acid acceptor such as potassium t-butoxide at room temperature and then preferably, slowly adding the dichloride reactant thereto, preferably in solution with a solvent, for example, THF, at a temperature below about 15 C. for control. However, the oxime reactant can be used in place of the salt, preferably in the presence of the acid acceptor. The resulting product is recovered and purified by standard procedure. For example, the resulting product can be recovered from the reaction mixture and purified from the reaction mixture by adding the mixture to a non-polar solvent such as benzene. The benzene mixture is then washed with water, dilute NaOH solution and then again by Water. The benzene is evaporated after the water has been removed, for example, by treatment with anhydrous MgSO to yield the purified product.

Reaction I(b) is carried out by reacting preferably equal mole amounts of the two reactants. If an excess of either reactant is used, the reaction still proceeds but yields are reduced. The reactants can be combined in any manner but preferably the. phosphorus-containing reactant is slowly added to the reactant containing the -SH group in a solvent such as THF, preferably with stirring. More preferably, an alkali metal salt of this reactant is used to reduce the chance of a violent reaction. The temperature of the reaction is not critical; however, better yields are obtained by heating the reactants at reflux for a time sufiicient to allow completion of the reaction. The resulting product can be recovered from the reaction mixture and purified by standard procedures. For example, the desired reaction product can be recovered from the reaction mixture by adding the mixture to a non-polar solvent such as benzene. The benzene mixture is then washed with water, dilute NaOH solution and then again by water. The benzene is evaporated after the water has been removed, for example, by treatment with anhydrous MgSO, to yield the purified product.

The process of this invention is represented by reaction II(a) and gives intermediate compounds useful to prepare the compounds of this invention. In other words, the process of this invention is a process for preparing a compound having the formula SSH in which R, R and R are as defined comprising reacting a compound of the formula in which R and R are as defined with a compound of the formula in which R is as defined.

The process of this invention is carried out by merely reacting preferably, about 2 moles of the oxime reactant with preferably about one mole of the thionophosphine sulfide reactant. If difierent proportions of either reactant are used, the reaction still proceeds but yields are lowered. The reactants can be combined in any desired manner. The reaction readily proceeds at room temperature and preferably is run under anhydrous conditions in a common solvent for the reactants such as benzene. The dithiophosphonic acid product can be recovered from its solvents in pure form, but it is preferred not to do so. If prolonged storage of the compound is desired, it is preferable to prepare either the alkali, alkaline or heavy metal salt of the acid.

Another process of this invention is represented by Reaction 110)) which utilizes as a reactant the product of Reaction II(a) preferably as a solution in the solvent utilized for Reaction II(a).

In this process, the reaction is carried out by reacting preferably about equal mole amounts of the reactants. If an excess of either reactant is used, the reaction still proceeds but again yields are lowered. Although the reactants can be combined in any desired manner, it is preferred to add the halide reactant to a solution of the dithiophosphonic acid reactant, preferably the acid is not recovered from the solvent in which it is prepared. Preferably, the reaction is carried out at below room temperature about -20" C. for control and in the presence of a base, such as triethyl amine, to take up the liberated acid reaction product. The reaction product is recovered by conventional means such as described for Reaction I(b).

Preferably, Reaction HI(a) is carried out by preparing and adding chloro-Z-propanone to a solution of an excess of the mercaptan reactant in the presence of an HCl acceptor at such at rate that the temperature does not exceed about 30 C. Thereafter, the mixture is heated to about 45 C. with stirring until the reaction is complete. The product is recovered by conventional techniques.

Preferably, Reaction III(b) is carried out by merely stirring at near room temperature for about 1 hour a mixture of about equal amounts of the two reactants dissolved in 10% ethanol solution after an aqueous solution of a base, such as sodium carbonate in water which had been slowly added over a period of about 20 minutes. The product is again recovered by conventional techniques.

The novel intermediate compounds of this invention which are (1) useful in preparing the compounds of this invention, for example, by Reaction II(b), heretofore described or (2) as insecticides or acaricides, are those having the formula R 3 SH C=N0i R R in which R is 1) alkyl having 1 to 8 carbon atoms, preferably branched chained, more preferably methyl and t-butyl or (2) lower alkylthiomethyl having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms; R is alkyl having 1 to 4 carbon atoms, preferably methyl and R is alkyl having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms.

These intermediate compounds are preparable according to Reaction II(a) and the subsequent discussion thereof.

If desired, the alkali, alkaline earth or heavy metal salts of the intermediate acid compounds can be prepared by conventional techniques such as by reacting the acid with a base. The salts will either be mono, di or tri basic depending upon the valency of the metal atom used to form the salt.

Preparation of the compounds of this invention, the process for preparing intermediates and the intermediates are illustrated in the following examples.

EXAMPLE I C=N 0 P N- (acetoneoximino), ethyl-dithiophosphonic acid This example teaches the synthesis of the oximino, ethyl phosphonic acid useful in the preparation of the compounds of this invention.

24.8 grams (0.1 mole) of ethylthionophosphine sulfide is combined with 200 ml. of anhydrous benzene in a 1000 ml. beaker. The mixture is magnetically stirred at room temperature, and 22.0 grams (0.3 mole) of acetoneoxime is added and the resulting mixture is stirred for 30 minutes until a clear solution is obtained. The benzene is evaporated to yield the desired product. N =1.5507.

EXAMPLE II O-(acetoneoximino) ethyl-S-methylphosphonothioate 24.8 grams (0.1 mole) of ethylthionophosphine sulfide is combined with 200 ml. of anhydrous dioxane in a 600 ml. beaker. The mixture is magnetically stirred at room temperature and 22.0 grams (0.3 mole) of acetoneoxime is added and the resulting mixture is stirred for 30 minutes until a clear solution containing the compound of Example I is obtained.

The solution is cooled in an ice bath to C., and 42.5 grams (0.3 mole) of methyliodide is added, followed by the addition of 30.3 grams (0.3 mole) of triethylamine over a period of 10 minutes, so that the temperature of the reaction does not exceed 20 C. The resulting mixture is stirred at room temperature for one hour, then poured into 500 m1. of benzene. The benzene mixture is washed 104 grams (1.0 mole) of the methylmercapto-Z-propanone, 83.5 grams (1.2 moles) of hydroxylamine hydrochloride, 400 ml. of water and 40 ml. of ethanol are combined in a 1 liter three-neck flask equipped with a stirrer, thermometer and dropping funnel. The mixture is stirred at room temperature, and a solution of 62 grams (0.5 mole) of sodium carbonate monohydrate in 150 ml. of H 0 is added over a period of 30 minutes. The resulting mixture is stirred at room temperature for one hour and then poured into 1 liter of benzene. The benzene phase is 10 with 200 ml. of H O, 100 ml. of saturated NaHCO soluseparated, drled with anhydrous MgSO and evaporated to tion followed by two 100 portions of H 0. The benzene yield 98 grams 82.3% of theory) of methylmercapto-Z- phase is dried with anhydrous MgSO and evaporated propanoneoxime. N =1.5190. under reduced pressure to yield 40.8 grams (99% of theory) of the desired compound. N =1.5500. The struc- EXAMPLE IV ture is confirmed by IR and NMR. 011380111 8 EXAMPLE III 5 cnsscrr, C

C=N 0 H 0- (methylthroacetogfiggmagafiilggfi methylthiomethyl) cm 12.4 grams (0.05 mole of ethylthiophosphine sulfide, Methyl mercnpto-2-propanoneoximlne 11.9 grams (0.1 mole) of methylmercapto-2-propanoneoxime of Example I and 200 ml. of dioxane are combined example feaches the SYPthe-SIS of the alkylthlo' in a 1 liter beaker and stirred magnetically at room temf f the Preparatlon of the compounds of perature until a solution is obtained. The solution is stirred thls lnventlonand cooled to 10 C. in an ice bath. 9.7 grams (0.1 mole) 202 grams F tnethylamme and 300 of chlorornethylmethylsulfide is added. Next, 15.1 grams of acetone are combined n a liter three-neck fiask (0.15 mole) of triethylamine is added Over a period of fl pp Wlth a cohdtillsel', stll'rel, thermometel: and drop 10 minutes. The resulting mixture is stirred at room tem- P g funRel-A11 0f methylmefcaptan 1S bubbled perature for 1 hour, then poured into 500 ml. of benzene into the stirring solution at room temperature. To the red consecutively i h d i 200 1 f water, 100 Sllhing mixture is added 185 grams moles) of chloro' ml. of saturated sodium bicarbonate solution and two 100 -p p at such a fate fi m p does 11f)! ml. portions of water. The benzene phase is dried with exceed 30 C. After the addition 18 completed, the IIllX- anhydrous MgSO and evaporated to yield 27 grams (89% ture is stirred and heated to C. for 15 minutes. The 35 f h f th d si d compound, N =1' 5937 t fi is Cooled, POUfed into 500 IIllof benzene, and The following is a table of certain selected compounds s e With two 0 Portions of Watef- The beIlZeIle that are preparable according to the procedure described Phase is dried With anhydrous 8 4 and evaporated to hereto. Compound numbers are assinged to each comyield 165.5 grams (81% of theory) of methylmercapto-Z- pound and are used throughout the remainder of the propanone. N "=1.4780. application.

TABLE I R\ lSI/S (LHzli.

C=NOP Compound M.P. C. Number or Np R R1 R1 R8 1 Semi-solid (CHahCHCH: CH; CzHs '0 (J}NHCH| 2 1.5840 CH; CH: 01H --SCHs 3 62-66 0H; CH; 01H; (1)

-NHz

4 1.5923 CH: CH: CzHs (H) N\ 5 1.5978 CH; CH: 02H, Q

e 1.5356 CH; CH; 01H CH=CC1: 7 1.5507 CH; CH. 01H; -C=N I 8 1.6043 CH: CH: 02H] SQ 9 1.5536 0H, 0H; 01H; CECH 10 1. 5845 CH; CH; 01H;

See footnotes at end of table.

this solution were combined with 1 milliliter of an acetone-peanut oil solution in an aluminum dish and allowed to dry. The aliquots were there to achieve desired toxicant concentration ranging from 100 ,ug. per dish to that at which 50% mortality was attained. The dishes were placed in a circular cardboard cage, closed on the bottom with cellophane and covered on top with cloth netting. Twenty-five female houseflies, three to five days old, were introduced into the cage and the percent mortality was recorded after 48 hours. The LD values are expressed in terms of pg. per 25 female flies. The results of these insecticidal evaluation tests are given in Table II under HF.

In the German Cockroach (GR) tests, one-month old nymphs were placed in separate circular cardboard cages sealed on one end with cellophane and covered by a cloth netting on the other. Aliquots of the toxicants, dissolved in an appropriate solvent, were diluted in water containing 0.002% of a wetting agent. Sponto 221 (a polyoxyether of alkylated phenols blended with organic sulfonates). Test concentrations ranged from 0.1% downward to that at which 50% mortality was obtained. Each of the aqueous suspensions of the candidate compounds was sprayed onto the insects through the cloth nettings by means of a hand-spray gun. Percent mortality in each case was recorded after 72 hours, and the LD values, expressed as percent of toxicant in the aqueous spray, were recorded. These values are reported under the column GR in Table II.

For testing the Salt Marsh Caterpillar, test solutions were prepared in an identical manner and at concentrations the same as for the German Cockroach above. Sections of bitter dock (Rumex obtusifolus) leaves, 1-1.5 inches in length were immersed in the test solutions for 10 to seconds and placed on a wire screen to dry. The dried leaf was placed on a moistened piece of filter paper in a Petri dish and infested with 5 3rd Instar larvae. Mortality of the larvae was recorded after 72 hours and the LD values are expressed as percent active ingredient in the aqueous suspension.

The Lygus Bug (LB) Lygus hesperus was tested similarly as the German Cockroach. The caged insects were sprayed with the candidate compounds at concentrations ranging from 0.05% downward to that at which 50% mortality was obtained. After twenty-four and seventytwo hours, counts were made to determine living and dead insects. The LD (percent) values were calculated. These values are reported under the column LB in Table II.

The insect species black bean aphid (BA) Aphz's fabae (Scop.) was also employed in the test for insecticidal activity. Young nasturtium (Tropaeolum sp.) plants, approximately 2 to 3 inches tall, were used as the host plants for the bean aphid. The host plant was infested with approximately 50-75 of the aphids. The test chemical was dissolved in acetone, added to water which contained a small amount of Sponto 221, an emulsifying agent. The solution was applied as a spray to the infested plants. Concentrations ranged from 0.05 percent downward until an LD value was achieved. These results are given in Table II under the column BA.

ACARICIDAL EVALUATION TEST The two-spotted mite (28M), Tetranychus urticae (Koch), was employed in tests for miticides. Young pinto bean plants or lima bean plants (Phaseolius sp.) in the primary leaf stage were used as the host plants. The young pinto bean plants were infested with about 100 mites of various ages. Dispersions of candidate materials were prepared by dissolving 0.1 gram in 10 ml. of a suitable solvent, usually acetone. Aliquots of the toxicant solutions were suspended in Water containing 0.002% v./v. Sponto 221, polyoxyethylene ether sorbitan monolaurate, an emulsifying agent, the amount of water being sufiicient to give concentrations of active ingredient ranging from 0.05% to that at which 50% mortality was obtained. The test suspensions were then sprayed on the infested plants to the point of run off. After seven days, mortalities of post-embryonic and ovicidal forms were determined. The percentage of kill was determined by comparison with control plants which had not been sprayed with the dancidate compounds. The LD values were calculated using well known procedures. These values are reported under the columns ZSM-PE and 2SM- Eggs in Table H.

SYSTEMATIC EVALUATION TEST This test evaluates the root absorption and upward translocation of the candidate systemic compound. The two-spotted mite (28M), Tetranychus urticae (Koch) and the Bean Aphid (BA), Aphis fabwe (Scop.) were employed in the test for systemic activity.

Young pinto bean plants in the primary leaf stage were used as host plants for the two-spotted mite. The pinto bean plants were placed in bottles containing 200 ml. of the test solution and held in place with cotton plugs. Only the roots were immersed. The test solutions were prepared by dissolving the compounds to be tested in a suitable solvent, usually acetone, and then diluting with distilled water. The final acetone concentration never exceeded about 1 percent. The toxicants were initially tested at a concentration of 10 parts per million (p.p.m.). Immediately after the host plant was placed in the test solution it was infested with the test species. Mortalities were determined after seven days.

Young nasturtium plants were used as the host plants for the bean aphid. The host plants were transplanted into one pound of soil that had been treated with the candidate compound. Immediately after planting in the treated soil the plants were infested with the aphids. Concentrations of toxicant in the soil ranged from 10 p.p.m.

per pound of soil downward until an LD value was obtained. Mortality was recorded after 72 hours.

The percentage of kill of each test species was determined by comparison with control plants placed in distilled water or untreated soil. The LD values were calculated. These systemic test results are reported in Table II under the columns BA-sys and ZSM-sys.

TABLE IL-LDao VALUES Two-spotted mites Com onnd HF, GR, SMC, BA, BA-sys, PE, Eggs, Sys, Num er g. percent percent percent percent p.p.m percent percent p.p.m.

See footnotes at end of table.

Sys, ppm.

TABLE IL-LDm VALUES Two-spotted mites HF, GR, LB, SMC, BA, BA-sys, PE, Eggs, g. percent percent percent percent p.p.rn. percent percent Compound Number s mirmmmdm 0 1111111131311815111111111111588588111881111151111118 1 I u a -losoc-oa -e- .u.. oh

Chemie," 4 Aufl.,

Bd XII/I, (1963), QDZSSH'I, pp. 423, 544, 583, 585, 586, 590.

I claim: 1. A compound having the formula B\ fi sH C=NOP R= in which R is (1) alkyl having 1 to 8 carbon atoms; or (2) lower alkylthiomethyl having 1 to 4 carbon atoms; R is alkyl having 1 to 4 carbon atoms; and R is alkyl 50 having 1 to 4 carbon atoms. 7

2. A compound of claim 1 which R is alkyl having 1 to 4 carbon atoms, R is methyl and R is alkyl having 1 to 2 carbon atoms.

References Cited UNITED STATES PATENTS 3,551,529 12/1970 Kargers 3,536,789 /1970 Lorenz et al. 3,652,736 3/1972 Gutman 3,666,839 5/1972 Gutman 260944 OTHER REFERENCES Houben-Weyl, Methoden der organ.

LEON ZITVER, Primary Examiner J. E. EVANS, Assistant Examiner us. c1. X.R.

Compound prepared in Example I. As those in the art are well aware, various techniques are available for incorporating the active component or Liquid compositions are also useful and normally comprise a dispersion of the toxicant in a liquid medium,

toxicant in suitable pesticidal compositions. Thus, the pesticidal compositions can be conveniently prepared in the form of liquids or solids, the latter preferably as homogeneous free-flowing dusts commonly formulated by admixing the active component with finely divided solids or carriers as exemplified by talc, natural clays, diatomaceous earth, various flours such as walnut shell, wheat, soya bean, cottonseed and so forth.

although it may be convenient to dissolve the toxicant directly in a solvent such as kerosene, fuel oil, xylene, alkylated naphthalenes or the like and use such organic solutions directly. However, the more common procedure is to employ dispersions of the toxicant in an aqueous medium and such compositions may be produced by forming a concentrated solution of the toxicant in a suitable organic solvent followed by'dispersion in water, usually with the aid of surface active agents. The latter, which may be the anionic, cationic, or monionic types, are exemplified by sodium stearate, potassium oleate and other alkaline metal soaps and detergents such as sodium lauryl sulfate, sodium naphthalene sulfonate, sodium alkyl naphthalane, sulfonate, methyl cellulose, fatty alcohol ethers, polyglycol fatty acid esters and other polyoxyethylene surface active agents. The proportion of these agents commonly comprises 1-15% by weight of the pesticidal compositions although the proportion is not critical and may be varied to suit any particular situation. 

